Allergic rhinitis is a common disorder and the number of patients is steadily increasing. The disease is caused by ambient airborne allergens, which cause an allergic inflammation within the nasal mucosa and it is often accompanied by conjunctivitis. According to the allergen, the allergic rhinitis is subdivided into seasonal allergic rhinitis (allergens like grass pollen, cedar pollen) and perennial allergic rhinitis (indoor allergens like mould, allergens from animals and house dust mite). Allergic rhinitis has a great impact on the quality of life. The patients suffer from an itchy and running nose, nasal blockage, headache and fatigue. Allergic conjunctivitis is often linked to allergic rhinitis and requires co-treatment. The major symptoms of conjunctivitis are burning and itching eyes and lacrimation. The basic mechanisms involved in this disease are the same as for allergic rhinitis.
The current treatment of allergic rhinitis is mainly focused on symptomatic relief. Oral and to a lesser extent topical antihistamines are the most widely used remedies. Oral antihistamines alleviate the histamine driven symptoms only. Allergen contact causes degranulation of mucosal mast cells and histamine is released. Histamine is responsible for the itching and sneezing and the increase in nasal secretion. Antihistamines block the binding of histamine to the histamine-H1-receptor and thereof the histamine mediated symptoms. Beside this obvious pathway, the allergens cause an eosinophilic inflammation of the nasal mucosa, which is mainly responsible for symptoms like nasal hyperreactivity, nasal blockage and the fear of the so called change of floors, which means that an untreated allergic rhinitis can develop to sinusitis and asthma bronchiale.
Treatment with glucocorticoids is currently the only one therapy, which targets the underlying allergic inflammation. To avoid systemic side effects typically for glucocorticoids, e.g. immunosuppression, reduced protein synthesis, impaired growth in children, topical treatment with glucocorticoids is the preferred way of administration.
A disadvantage of nasal steroids is the slow onset of action and the need for continuous treatment. It takes 4-6 days of continuous treatment before a symptom relief can be observed. Therefore, the patients are recommended to begin to take glucocorticoids before the pollen season starts. The slow onset of action, the need of consequent treatment and the fear of steroid induced side effects have a negative impact on the use of intranasal steroids and patient's compliance.
Other medications available for the treatment are just for symptomatic relief, for example intranasal muscarinic antagonists (ipratropium to reduce nasal secretion), adrenoreceptor agonists (xylomethazoline to reduce nasal congestion).
WO 97/01337 describes a nasal spray or nasal drops formulation comprising beclomethasone, flunisolide, triamcinolone, dexamethasone or budesonide in combination with the antihistamines levocabastine, azelastine or azatadine and sterile water.
WO 97/46243 is related to a nasal spray containing an intranasal steroid and an antihistamine.
WO 98/48839 is related to topically applicable nasal compositions comprising a therapeutically effective amount of an antiinflammatory agent and a therapeutically effective amount of at least one agent selected from the group consisting of a vasoconstrictor, a neuraminidase inhibitor, a leukotriene inhibitor, an antihistamine, an antiallergic agent, an anticholinergic agent, an anesthetic and a mucolytic agent.
WO 01/22955 is related to a novel combination of loteprednol, a so-called soft steroid with antihistamines.
WO 03/049770 discloses compositions and methods for treating rhinitis with H1 antagonists/antiallergics and safe steroids.
U.S. Pat. No. 5,164,194 is related to nasal formulations for azelastine.